How Immunotherapy Is Changing Cancer Care
Chemotherapy attacks the cancer. Immunotherapy does something different: it removes the brakes the cancer has applied to your immune system, so the immune system can attack it instead.
The checkpoint problem
Your immune system has built-in brakes — checkpoints — that stop it attacking healthy tissue. Without them, autoimmune disease results.
Many tumours survive by exploiting those brakes. A cancer cell displaying the PD-L1 protein engages the PD-1 receptor on an approaching T-cell, which is read as "leave this cell alone". The T-cell stands down. The tumour is not hidden; it is protected.
What checkpoint inhibitors do
Checkpoint inhibitors are antibodies that block that handshake. Three targets are in wide clinical use:
- PD-1 — pembrolizumab, nivolumab, cemiplimab
- PD-L1 — atezolizumab, durvalumab, avelumab
- CTLA-4 — ipilimumab, tremelimumab
Blocking the interaction restores the T-cell's ability to recognise and kill the tumour cell. The drug does not attack the cancer itself — the immune system does.
Why responses can be durable
This is the property that distinguishes immunotherapy. Where it works, responses can persist for years, sometimes continuing after treatment stops, because the immune system retains memory of what it learned to attack.
In melanoma and some lung cancers, this has produced long-term survival in a subset of patients with advanced disease — an outcome that was essentially unavailable before.
Why it does not work for everyone
Response rates for single-agent checkpoint inhibition typically run around 20-40%, depending heavily on cancer type. Predicting who will respond is imperfect. Biomarkers that help include:
- PD-L1 expression on the tumour
- Tumour mutational burden — heavily mutated tumours look more foreign
- Microsatellite instability / mismatch repair deficiency — a strong predictor across tumour types
None is definitive. Some patients with high PD-L1 do not respond; some with none do.
Immune-related adverse events
The side effect profile is unlike chemotherapy's. Releasing the brakes can allow the immune system to attack healthy tissue, producing inflammation anywhere:
- Skin — rash, itching
- Gut — colitis, which can be severe
- Endocrine — thyroid, pituitary or adrenal dysfunction, often permanent
- Liver — hepatitis
- Lung — pneumonitis
- Less commonly: heart, kidney, nervous system
Two things make these different from chemotherapy side effects. They can appear weeks or months after treatment, including after it has finished. And they are treated by suppressing the immune response — usually corticosteroids — rather than by waiting.
Anyone on a checkpoint inhibitor should carry an alert card, and any new symptom should be reported rather than watched. An emergency department that does not know a patient is on immunotherapy may misread colitis as gastroenteritis.
Combinations and where the field is going
Checkpoint inhibitors are increasingly combined with chemotherapy, with targeted therapy, or with each other. Combining PD-1 and CTLA-4 blockade increases response rates and also increases toxicity, so it is a considered trade-off.
Beyond checkpoints, cell therapies such as CAR-T have produced striking results in some blood cancers, and bispecific antibodies that physically bridge a T-cell to a tumour cell are expanding quickly.
For biomarker-driven treatment in a specific setting, see our guide to targeted therapy in lung cancer. Browse the oncology catalogue.
This article is general information, not medical advice. Treatment decisions belong with a qualified clinician who knows your history. Every medicine mentioned is prescription-only and requires a valid prescription.
